document_title: Histone acetylation and deacetylation

question_text: what chemical changes in histone proteins are responsible for changes in gene expression

text: Histone acetylation and deacetylation

text: Mechanism of action[edit]

text: Nucleosomes are portions of double-stranded DNA (dsDNA) that are wrapped around protein complexes called histone cores. These histone cores are composed of 8 subunits, two each of H2A, H2B, H3 and H4 histones. This protein complex forms a cylindrical shape that dsDNA wraps around with approximately 147 base pairs. Nucleosomes are formed as a beginning step for DNA compaction that also contributes to structural support as well as serves functional roles.[2] These functional roles are contributed by the tails of the histone subunits. The histone tails insert themselves in the minor grooves of the DNA and extend through the double helix,[1] which leaves them open for modifications involved in transcriptional activation.[3] Acetylation has been closely associated with increases in transcriptional activation while deacetylation has been linked with transcriptional deactivation. These reactions occur post-translation and are reversible.[3]

text: The mechanism for acetylation and deacetylation takes place on the NH3+ groups of Lysine amino acid residues. These residues are located on the tails of histones that make up the nucleosome of packaged dsDNA. The process is aided by factors known as Histone Acetyltransferases (HATs). HAT molecules facilitate the transfer of an acetyl group from a molecule of Acetyl Coenzyme-A (Acetyl-CoA) to the NH3+ group on Lysine. When a Lysine is deacetylated, factors known as Histone Deacetylases (HDACs) catalyze the removal of the acetyl group with a molecule of H2O.[3][4]

text: Acetylation has the effect of changing the overall charge of the histone tail from positive to neutral. Nucleosome formation is dependent on the positive charges of the H4 histones and the negative charge on the surface of H2A histone fold domains. Acetylation of the histone tails disrupts this association, leading to weaker binding of the nucleosomal components.[1] By doing this, the DNA is more accessible and leads to more transcription factors being able to reach the DNA. Thus, acetylation of histones is known to increase the expression of genes through transcription activation. Deacetylation performed by HDAC molecules has the opposite effect. By deacetylating the histone tails, the DNA becomes more tightly wrapped around the histone cores, making it harder for transcription factors to bind to the DNA. This leads to decreased levels of gene expression and is known as gene silencing.[5][6][7]

text: Acetylated histones, the octomeric protein cores of nucleosomes, represent a type of epigenetic marker within chromatin. Studies have shown that one modification has the tendency to influence whether another modification will take place. Modifications of histones can not only cause secondary structural changes at their specific points, but can cause many structural changes in distant locations which inevitably affects function.[8] As the chromosome is replicated, the modifications that exist on the parental chromosomes are handed down to daughter chromosomes. The modifications, as part of their function, can recruit enzymes for their particular function and can contribute to the continuation of modifications and their effects after replication has taken place.[1] It has been shown that, even past one replication, expression of genes may still be affected many cell generations later. A study showed that, upon inhibition of HDAC enzymes by Trichostatin A, genes inserted next to centric heterochromatin showed increased expression. Many cell generations later, in the absence of the inhibitor, the increased gene expression was still expressed, showing modifications can be carried through many replication processes such as mitosis and meiosis.[8]

text: Histone acetylation/deacetylation enzymes[edit]

text: Histone acetyltransferase (HATs)[edit]

text: Histone Acetyltransferases, also known as HATs, are a family of enzymes that acetylate the histone tails of the nucleosome. This, and other modifications, are expressed based on the varying states of the cellular environment.[2] Many proteins with acetylating abilities have been documented and, after a time, were categorized based on sequence similarities between them. These similarities are high among members of a family, but members from different families show very little resemblance.[9] Some of the major families identified so far are as follows.

text: GNAT family[edit]

text: General Control Non-Derepressible 5 (Gcn5) –related N-Acetyltransferases (GNATs) is one of the many studied families with acetylation abilities.[10] This superfamily includes the factors Gcn5 which is included in the SAGA, SLIK, STAGA, ADA, and A2 complexes, Gcn5L, p300/CREB-binding protein associated factor (PCAF), Elp3, HPA2 and HAT1.[10][11] Major features of the GNAT family include HAT domains approximately 160 residues in length and a conserved bromodomain that has been found to be an acetyl-lysine targeting motif.[9] Gcn5 has been shown to acetylate substrates when it is part of a complex.[11] Recombinant Gcn5 has been found to be involved in the acetylation of the H3 histones of the nucleosome.[2][11] To a lesser extent, it has been found to also acetylate H2B and H4 histones when involved with other complexes.[2][3][11] PCAF has the ability to act as a HAT protein and acetylate histones, it can acetylate non-histone proteins related to transcription, as well as act as a coactivator in many processes including myogenesis, nuclear-receptor-mediated activation and growth-factor-signaled activation. Elp3 has the ability to acetylate all histone subunits and also shows involvement in the RNA polymerase II holoenzyme.[2]

text: MYST family[edit]

text: MOZ (Monocytic Leukemia Zinc Finger Protein), Ybf2/Sas3, Sas2 and Tip60 (Tat Interacting Protein) all make up MYST, another well known family that exhibits acetylating capabilities. This family includes Sas3, essential SAS-related acetyltransferase (Esa1), Sas2, Tip60, MOF, MOZ, MORF, and HBO1. The members of this family have multiple functions, not only with activating and silencing genes, but also affect development and have implications in human diseases.[11] Sas2 and Sas3 are involved in transcription silencing, MOZ and TIF2 are involved with the formation of leukemic transclocation products while MOF is involved in dosage compensation in Drosophila. HAT domains for this family are approximately 250 residues which include cysteine-rich, zinc binding domains as well as N-terminal chromodomains. The MYST proteins Esa1, Sas2 and Sas3 are found in yeast, MOF is found in Drosophila while Tip60, MOZ, MORF, and HBO1 are found in humans.[9] Tip60 has roles in the regulation of gene transcription, HBO has been found to impact the DNA replication process, MORF is able to acetylate free histones (especially H3 and H4) as well as nucleosomal histones.[2]

text: p300/CBP family[edit]

text: Adenoviral E1A-associated protein of 300kDa (p300) and the CREB-binding protein (CBP) make up the next family of HATs.[10] This family of HATs contain HAT domains that are approximately 500 residues long and contain bromodomains as well as three cysteine-histidine rich domains that help with protein interactions.[9] These HATs are known to acetylate all of the histone subunits in the nucleosome. They also have the ability to acetylate and mediate non-histone proteins involved in transcription and are also involved in the cell-cycle, differentiation and apoptosis.[2]

text: Other HATs[edit]

text: There are other proteins that have acetylating abilities but differ in structure to the previously mentioned families. One HAT is called steroid receptor coactivator 1 (SRC1), which has a HAT domain located at the C-terminus end of the protein along with a basic helix-loop-helix and PAS A and PAS B domains with a LXXLL receptor interacting motif in the middle. Another is ATF-2 which contains a transcriptional activation (ACT) domain and a basic zipper DNA-binding (bZip) domain with a HAT domain in-between. The last is TAFII250 which has a Kinase domain at the N-terminus region, two bromodomains located at the C-terminus region and a HAT domain located in-between.[12]

text: Histone deacetylase (HDACs)[edit]

text: There are a total of four classes that categorize Histone Deacetylases (HDACs). Class I includes HDACs 1, 2, 3, and 8. Class II is divided into two subgroups, Class IIA and Class IIB. Class IIA includes HDACs 4, 5, 7, and 9 while Class IIB includes HDACs 6 and 10. Class III contains the Sirtuins and Class IV contains only HDAC11.[5][6] Classes of HDAC proteins are divided and grouped together based on the comparison to the sequence homologies of Rpd3, Hos1 and Hos2 for Class I HDACs, HDA1 and Hos3 for the Class II HDACs and the sirtuins for Class III HDACs.[6]

text: Class I HDACs[edit]

text: HDAC1 & HDAC2[edit]

text: HDAC1 & HDAC2 are in the first class of HDACs are most closely related to one another.[5][6] By analyzing the overall sequences of both HDACs, their similarity was found to be approximately 82% homologous.[5] These enzymes have been found to be inactive when isolated which led to the conclusion that they must be incorporated with cofactors in order to activate their deacetylase abilities.[5] There are three major protein complexes that HDAC 1 & 2 may incorporate themselves into. These complexes include Sin3 (named after its characteristic protein mSin3A), Nucleosome Remodelling and Deacetylating complex (NuRD), and Co-REST.[5][6] The Sin3 complex and the NuRD complex both contain HDACs 1 and 2, the Rb-associated protein 48 (RbAp48) and RbAp46 which make up the core of each complex.[2][6] Other complexes may be needed though in order to initiate the maximum amount of available activity possible. HDACs 1 and 2 can also bind directly to DNA binding proteins such as Yin and Yang 1 (YY1), Rb binding protein 1 and Sp1.[5] HDACs 1 and 2 have been found to express regulatory roles in key cell cycle genes including p21.[6]

text: Activity of these HDACs can be affected by phosphorylation. An increased amount of phosphorylation (hyperphosphorylation) leads to increased deacetylase activity, but degrades complex formation between HDACs 1 and 2 and between HDAC1 and mSin3A/YY1. A lower than normal amount of phosphorylation (hypophosphorylation) leads to a decrease in the amount of deacetylase activity, but increases the amount of complex formation. Mutation studies found that major phosphorylation happens at residues Ser421 and Ser423. Indeed, when these residues were mutated, a drastic reduction was seen in the amount of deacetylation activity.[5] This difference in the state of phosphorylation is a way of keeping an optimal level of phosphorylation to ensure there is no over or under expression of deacetylation. HDACs 1 and 2 have been found only exclusively in the nucleus.[2][6] In HDAC1 knockout (KO) mice, mice were found to die during embryogenesis and showed a drastic reduction in the production but increased expression of Cyclin-Dependent Kinase Inhibitors (CDKIs) p21 and p27. Not even upregulation of the other Class I HDACs could compensate for the loss of HDAC1. This inability to recover from HDAC1 KO leads researchers to believe that there are both functional uniqueness to each HDAC as well as regulatory cross-talk between factors.[6]

text: HDAC3 has been found to be most closely related to HDAC8. HDAC3 contains a non-conserved region in the C-terminal region that was found to be required for transcriptional repression as well as its deacetylase activity. It also contains two regions, one called a Nuclear Localization Signal (NLS) as well as a Nuclear Export Signal (NES). The NLS functions as a signal for nuclear action while an NES functions with HDACs that perform work outside of the nucleus. A presence of both signals for HDAC3 suggests it travels between the nucleus and the ctyoplasm.[5] HDAC3 has even been found to interact with the plasma membrane.[6] Silencing Mediator for Retinoic Acid and Thyroid Hormone (SMRT) receptors and Nuclear Receptor Co-Repressor (N-CoR) factors must be utilized by HDAC3 in order to activate it.[5][6] Upon doing so, it gains the ability to co-precipitate with HDACs 4, 5, and 7. HDAC3 can also be found complexed together with HDAC-related protein (HDRP).[5] HDACs 1 and 3 have been found to mediate Rb-RbAp48 interactions which suggests that it functions in cell cycle progression.[5][6] HDAC3 also shows involvement in stem cell self-renewal and a transcription independent role in mitosis.[6]

text: HDAC8 has been found to be most similar to HDAC3. Its major feature is its catalytic domain which contains an NLS region in the center. Two transcripts of this HDAC have been found which include a 2.0kb transcript and a 2.4kb transcript.[5] Unlike the other HDAC molecules, when purified, this HDAC showed to be enzymatically active.[6] At this point, due to its recent discovery, it is not yet known if it is regulated by co-repressor protein complexes. Northern blots have revealed that different tissue types show varying degrees of HDAC8 expression[5] but has been observed in smooth muscles and is thought to contribute to contractility.[6]

text: Class II HDACs[edit]

text: Class IIA[edit]

text: The Class IIA HDACs includes HDAC4, HDAC5, HDAC7 and HDAC9. HDACs 4 and 5 have been found to most closely resemble each other while HDAC7 maintains a resemblance to both of them. There have been three discovered variants of HDAC9 including HDAC9a, HDAC9b and HDAC9c/HDRP, while more have been suspected. The variants of HDAC9 have been found to have similarities to the rest of the Class IIA HDACs. For HDAC9, the splicing variants can be seen as a way of creating a "fine-tuned mechanism" for differentiation expression levels in the cell. Different cell types may take advantage and utilize different isoforms of the HDAC9 enzyme allowing for different forms of regulation. HDACs 4, 5 and 7 have their catalytic domains located in the C-terminus along with an NLS region while HDAC9 has its catalytic domain located in the N-terminus. However, the HDAC9 variant HDAC9c/HDRP lacks a catalytic domain but has a 50% similarity to the N-terminus of HDACs 4 and 5.[5]

text: For HDACs 4, 5 and 7, conserved binding domains have been discovered that bind for C-terminal binding protein (CtBP), myocyte enhancer factor 2 (MEF2) and 14-3-3.[5][6] All three HDACs work to repress the myogenic transcription factor MEF2 which an essential role in muscle differentiation as a DNA binding transcription factor. Binding of HDACs to MEF2 inhibits muscle differentiation, which can be reversed by action of Ca2+/calmodulin-dependent kinase (CaMK) which works to dissociate the HDAC/MEF2 complex by phosphorylating the HDAC portion.[5] They have been seen to be involved in cellular hypertrophy in muscle control differentiation as well as cellular hypertrophy in muscle and cartilage tissues.[6] HDACs 5 and 7 have been shown to work in opposition to HDAC4 during muscle differentiation regulation so as to keep a proper level of expression. There has been evidence that these HDACs also interact with HDAC3 as a co-recruitment factor to the SMRT/N-CoR factors in the nucleus. Absence of the HDAC3 enzyme has shown to lead to inactivity which makes researchers believe that HDACs 4, 5 and 7 help the incorporation of DNA-binding recruiters for the HDAC3-containing HDAC complexes located in the nucleus.[5] When HDAC4 is knocked out in mice, they suffer from a pronounced chondrocyte hypertrophy and die due to extreme ossification. HDAC7 has been shown to suppress Nur77-dependent apoptosis. This interaction leads to a role in clonal expansion of T cells. HDAC9 KO mice are shown to suffer from cardiac hypertrophy which is exacerbated in mice that are double KO for HDACs 9 and 5.[6]

text: Class IIB[edit]

text: The Class IIB HDACs include HDAC6 and HDAC10. These two HDACs are most closely related to each other in overall sequence. However, HDAC6's catalytic domain is most similar to HDAC9.[5] A unique feature of HDAC6 is that it contains two catalytic domains in tandem of one another.[5][6] Another unique feature of HDAC6 is the HDAC6-, SP3, and Brap2-related zinc finger motif (HUB) domain in the C-terminus which shows some functions related to ubiquitination, meaning this HDAC is prone to degradation.[5] HDAC10 has two catalytic domains as well. One active domain is located in the N-terminus and a putative catalytic domain is located in the C-terminus[5][6] along with an NES domain.[5] Two putative Rb-binding domains have also been found on HDAC10 which shows it may have roles in the regulation of the cell cycle. Two variants of HDAC10 have been found, both having slight differences in length. HDAC6 is the only HDAC to be shown to act on tubulin, acting as a tubulin deacetylase which helps in the regulation of microtubule-dependent cell motility. It is mostly found in the cytoplasm but has been known to be found in the nucleus, complexed together with HDAC11. HDAC10 has been seen to act on HDACs 1, 2, 3 (or SMRT), 4, 5 and 7. Some evidence has been shown that it may have small interactions with HDAC6 as well. This leads researchers to believe that HDAC10 may function more as a recruiter rather than a factor for deacetylation. However, experiments conducted with HDAC10 did indeed show deacetylation activity.[5]

text: Class IV HDACs[edit]

text: HDAC11 has been shown to be related to HDACs 3 and 8, but its overall sequence is quite different from the other HDACs, leading it to be in its own category.[5][6] HDAC11 has a catalytic domain located in its N-terminus. It has not been found incorporated in any HDAC complexes such as Nurd or SMRT which means it may have a special function unique to itself. It has been found that HDAC11 remains mainly in the nucleus.[5]

text: Biological functions[edit]

text: Transcription regulation[edit]

text: The discovery of histone acetylation causing changes in transcription activity can be traced back to the work of Vicent Allfrey and colleagues in 1964.[13] The group hypothesized that histone proteins modified by acetyl groups added negative charges to the positive lysines, and thus, reduced the interaction between DNA and histones.[14] Histone modification is now considered a major regulatory mechanism that is involved in many different stages of genetic functions.[15] Our current understanding is that acetylated lysine residues on histone tails is associated with transcriptional activation. In turn, deacetylated histones are associated with transcriptional repression. In addition, negative correlations have been found between several histone acetylation marks.[16]

text: The regulatory mechanism is thought to be twofold. Lysine is an amino acid with a positive charge when unmodified. Lysines on the amino terminal tails of histones have a tendency to weaken the chromatin's overall structure. Addition of an acetyl group, which carries a negative charge, effectively removes the positive charge and hence, reduces the interaction between the histone tail and the nucleosome.[17] This opens up the usually tightly packed nucleosome and allows transcription machinery to come into contact with the DNA template, leading to gene transcription.[18] Repression of gene transcription is achieved by the reverse of this mechanism. The acetyl group is removed by one of the HDAC enzymes during deacetylation, allowing histones to interact with DNA more tightly to form compacted nucleosome assembly. This increase in the rigid structure prevents the incorporation of transcriptional machinery, effectively silencing gene transcription.

text: Another implication of histone acetylation is to provide a platform for protein binding. As a posttranslational modification, the acetylation of histones can attract proteins to elongated chromatin that has been marked by acetyl groups. It has been hypothesized that the histone tails offer recognition sites that attract proteins responsible for transcriptional activation.[19] Unlike histone core proteins, histone tails are not part of the nucleosome core and are exposed to protein interaction. A model proposed that the acetylation of H3 histones activates gene transcription by attracting other transcription related complexes. Therefore, the acetyl mark provides a site for protein recognition where transcription factors interact with the acetylated histone tails via their bromodomain.[20]

text: Histone code hypothesis[edit]

text: The Histone code hypothesis suggests the idea that patterns of post-translational modifications on histones, collectively, can direct specific cellular functions.[21] Chemical modifications of histone proteins often occur on particular amino acids. This specific addition of single or multiple modifications on histone cores can be interpreted by transcription factors and complexes which leads to functional implications. This process is facilitated by enzymes such as HATs and HDACs that add or remove modifications on histones, and transcription factors that process and "read" the modification codes. The outcome can be activation of transcription or repression of a gene. For example, the combination of acetylation and phosphorylation have synergistic effects on the chromosomes overall structural condensation level and, hence, induces transcription activation of immediate early gene.[22]

text: Experiments investigating acetylation patterns of H4 histones suggested that these modification patterns are collectively maintained in mitosis and meiosis in order to modify long-term gene expression.[8] The acetylation pattern is regulated by HAT and HADC enzymes and, in turn, sets the local chromatin structure. In this way, acetylation patterns are transmitted and interconnected with protein binding ability and functions in subsequent cell generation.

text: Bromodomain[edit]

text: The bromodomain is a motif that is responsible for acetylated lysine recognition on histones by nucleosome remodelling proteins. Posttranslational modifications of N- and C-terminal histone tails attracts various transcription initiation factors that contain bromodomains, including human transcriptional coactivator PCAF, TAF1, GCN5 and CREB-binding protein(CBP), to the promoter and have a significance in regulating gene expression.[23] Structural analysis of transcription factors has shown that highly conserved bromodomains are essential for protein to bind to acetylated lysine.This suggests that specific histone site acetylation has a regulatory role in gene transcriptional activation.[24]

text: Human diseases[edit]

text: Inflammatory diseases[edit]

text: Gene expression is regulated by histone acetylation and deacetylation, and this regulation is also applicable to inflammatory genes. Inflammatory lung diseases are characterized by expression of specific inflammatory genes such as NF-κB and AP-1 transcription factor. Treatments with corticosteroids and theophylline for inflammatory lung diseases interfere with HAT/HDAC activity to turn off inflammatory genes.[25]

text: Specifically, gene expression data demonstrated increased activity of HAT and decreased level of HDAC activity in patients with Asthma.[26] Patients with chronic obstructive pulmonary disease showed there is an overall decrease in HDAC activity with unchanged levels of HAT activity.[27] Results have shown that there is an important role for HAT/HDAC activity balance in inflammatory lung diseases and provided insights on possible therapeutic targets.[28]

text: Cancer[edit]

text: Due to the regulatory role during transcription of epigenetic modifications in genes, it is not surprising that changes in epigenetic markers, such as acetylation, can contribute to cancer development. HDACs expression and activity in tumor cells is very different from normal cells. The overexpression and increased activity of HDACs has been shown to be characteristic of tumorigenesis and metastasis, suggesting an important regulatory role of histone deacetylation on oncogene expression.[29] One of the examples is the regulation role of histone acetylation/deacetylation in P300 and CBP, both of which contribute to oncogenesis.[30]

text: Approved in 2006 by the U.S. Food and Drug Administration (FDA), Vorinostat represents a new category for anticancer drugs that are in development. Vorinostat targets histone acetylation mechanisms and can effectively inhibit abnormal chromatin remodeling in cancerous cells. Targets of Vorinostat includes HDAC1, HDAC2, HDAC3 and HDAC6.[31][32]

text: Other disorders[edit]

text: Suggested by the idea that the structure of chromatin can be modified to allow or deny access of transcription activators, regulatory functions of histone acetylation and deacetylation can have implications with genes that cause other diseases. Studies on histone modifications may reveal many novel therapeutic targets.

text: Based on different cardiac hypertrophy models, it has been demonstrated that cardiac stress can result in gene expression changes and alter cardiac function.[33] These changes are mediated through HATs/HDACs posttranslational modification signaling. HDAC inhibitor trichostatin A was reported to reduce stress induced cardiomyocyte autophagy.[34] Studies on p300 and CREB-binding protein linked cardiac hypertrophy with cellular HAT activity suggesting an essential role of histone acetylation status with hypertrophy responsive genes such as GATA4, SRF, and MEF2.[35][36][37][38]

text: Epigenetic modifications also play a role in neurological disorders. Deregulation of histones modification are found to be responsible for deregulated gene expression and hence associated with neurological and psychological disorders, such as Schizophrenia[39] and Huntington disease.[40] Current studies indicate that inhibitors of the HDAC family have therapeutic benefits in a wide range of neurological and psychiatric disorders.[41] Many neurological disorders only affect specific brain regions, therefore, understanding of the specificity of HDACs is still required for further investigations for improved treatments.


document_title: Party leaders of the United States Senate

question_text: the official head of the senate is the

question_tokens: the official head of the senate is the

root

text: Current floor leaders[edit]

text: The Senate is currently composed of 51 Republicans, 47 Democrats, and 2 independents, both of whom caucus with the Democrats.

tag: p

text: The current leaders are long-time Senators Mitch McConnell (R) from Kentucky and Chuck Schumer (D) from New York. The current Assistant Leaders/Whips are long-time Senators John Cornyn (R) from Texas and Dick Durbin (D) from Illinois.

text: History[edit]

text: The Democrats began the practice of electing floor leaders in 1920 while they were in the minority. John W. Kern was a Democratic Senator from Indiana. While the title was not official, he is considered[by whom?] to be the first Senate party leader from 1913 through 1917 (and in turn, the first Senate Democratic Leader), while serving concurrently as Chairman of the Senate Democratic Caucus. In 1925 the majority (at the time) Republicans also adopted this language when Charles Curtis became the first (official) Majority Leader[citation needed], although his immediate predecessor Henry Cabot Lodge is considered the first (unofficial) Senate Majority Leader.

text: The Constitution designates the Vice President of the United States as President of the United States Senate. The Constitution also calls for a President pro tempore to serve as the leader of the body when the President of the Senate (the Vice President) is absent. In practice, neither the Vice President nor the President pro tempore—customarily the most senior (longest-serving) Senator in the majority party—actually presides over the Senate on a daily basis; that task is given to junior Senators of the majority party. Since the Vice President may be of a different party than the majority and is not a member subject to discipline, the rules of procedure of the Senate give the presiding officer very little power and none beyond the presiding role. For these reasons, it is the Majority Leader who, in practice, manages the Senate. This is in contrast to the House of Representatives where the elected Speaker of the House has a great deal of discretionary power and generally presides over votes on bills.[citation needed]

text: List of party leaders[edit]

text: The Democratic Party first selected a leader in 1920. The Republican Party first formally designated a leader in 1925.

text:
Cong-
ress
Dates
Democratic Whip
Democratic Leader
Majority
Republican Leader
Republican Whip

63rd
May 28, 1913 –
March 4, 1915
J. Hamilton Lewis
None
Democratic
← Majority
None
None

64th
March 4, 1915 –
December 6, 1915

December 6, 1915 –
December 13, 1915
James Wadsworth

December 13, 1915 –
March 4, 1917
Charles Curtis

65th
March 4, 1917 –
March 4, 1919

66th
March 4, 1919 –
April 27, 1920
Peter Gerry
Republican
Majority →
Henry Cabot Lodge
Unofficial

April 27, 1920 –
March 4, 1921
Oscar Underwood

67th
March 4, 1921 –
March 4, 1923

68th
March 4, 1923 –
December 3, 1923

December 3, 1923 –
November 9, 1924
Joseph Taylor Robinson

November 9, 1924 –
March 4, 1925
Charles Curtis
Acting
Wesley Jones
Acting

69th
March 4, 1925 –
March 4, 1927
Charles Curtis
Wesley Jones

70th
March 4, 1927 –
March 4, 1929

71st
March 4, 1929 –
March 4, 1931
Morris Sheppard
James E. Watson
Simeon Fess

72nd
March 4, 1931 –
March 4, 1933

73rd
March 4, 1933 –
January 3, 1935
J. Hamilton Lewis
Democratic
← Majority
Charles L. McNary
Felix Hebert

74th
January 3, 1935 –
January 3, 1937
None[Note 1]

75th
January 3, 1937 –
July 14, 1937

July 22, 1937 –
January 3, 1939
Alben W. Barkley

76th
January 3, 1939 –
April 9, 1939

April 9, 1939 –
January 3, 1940
Sherman Minton

January 3, 1940 –
January 3, 1941
Warren Austin
Acting

77th
January 3, 1941 –
January 3, 1943
J. Lister Hill
Charles L. McNary

78th
January 3, 1943 –
February 25, 1944
Kenneth Wherry

February 25, 1944 –
January 3, 1945
Wallace H. White Jr.
Acting

79th
January 3, 1945 –
January 3, 1947
Wallace H. White Jr.

80th
January 3, 1947 –
January 3, 1949
Scott W. Lucas
Republican
Majority →

81st
January 3, 1949 –
January 3, 1951
Francis Myers
Scott W. Lucas
Democratic
← Majority
Kenneth S. Wherry
Leverett Saltonstall

82nd
January 3, 1951 –
January 3, 1952
Lyndon B. Johnson
Ernest McFarland

January 3, 1952 –
January 3, 1953
Styles Bridges

83rd
January 3, 1953 –
July 31, 1953
Earle Clements
Lyndon B. Johnson
Republican
Majority →
Robert A. Taft

August 3, 1953 –
January 3, 1955
William F. Knowland

84th
January 3, 1955 –
January 3, 1957
Democratic
← Majority

85th
January 3, 1957 –
January 3, 1959
Mike Mansfield
Everett Dirksen

86th
January 3, 1959 –
January 3, 1961
Everett Dirksen
Thomas Kuchel

87th
January 3, 1961 –
January 3, 1963
Hubert Humphrey
Mike Mansfield

88th
January 3, 1963 –
January 3, 1965

89th
January 3, 1965 –
January 3, 1967
Russell B. Long

90th
January 3, 1967 –
January 3, 1969

91st
January 3, 1969 –
September 7, 1969
Ted Kennedy
Hugh Scott

September 24, 1969 –
January 3, 1971
Hugh Scott
Robert Griffin

92nd
January 3, 1971 –
January 3, 1973
Robert Byrd

93rd
January 3, 1973 –
January 3, 1975

94th
January 3, 1975 –
January 3, 1977

95th
January 3, 1977 –
January 3, 1979
Alan Cranston
Robert Byrd
Howard Baker
Ted Stevens

96th
January 3, 1979 –
November 1, 1979

November 1, 1979 –
March 5, 1980
Ted Stevens
Acting

March 5, 1980 –
January 3, 1981
Howard Baker

97th
January 3, 1981 –
January 3, 1983
Republican
Majority →

98th
January 3, 1983 –
January 3, 1985

99th
January 3, 1985 –
January 3, 1987
Bob Dole
Alan Simpson

100th
January 3, 1987 –
January 3, 1989
Democratic
← Majority

101st
January 3, 1989 –
January 3, 1991
George Mitchell

102nd
January 3, 1991 –
January 3, 1993
Wendell H. Ford

103rd
January 3, 1993 –
January 3, 1995

104th
January 3, 1995 –
June 12, 1996
Tom Daschle
Republican
Majority →
Trent Lott

June 12, 1996 –
January 3, 1997
Trent Lott
Don Nickles

105th
January 3, 1997 –
January 3, 1999

106th
January 3, 1999 –
January 3, 2001
Harry Reid

107th
January 3, 2001 –
January 20, 2001
Democratic
← Majority

January 20, 2001 –
June 6, 2001
Republican
Majority →

June 6, 2001 –
January 3, 2003[Note 2]
Democratic
← Majority

108th
January 3, 2003 –
January 3, 2005
Republican
Majority →
Bill Frist
Mitch McConnell

109th
January 3, 2005 –
January 3, 2007
Dick Durbin
Harry Reid

110th
January 3, 2007 –
December 18, 2007
Democratic
← Majority
Mitch McConnell
Trent Lott

December 19, 2007 –
January 3, 2009
Jon Kyl

111th
January 3, 2009 –
January 3, 2011

112th
January 3, 2011 –
January 3, 2013

113th
January 3, 2013 –
January 3, 2015
John Cornyn

114th
January 3, 2015 –
January 3, 2017
Republican
Majority →

115th
January 3, 2017 –
January 3, 2019
Chuck Schumer

Cong-
ress
Dates
Democratic Whip
Democratic Leader
Majority
Republican Leader
Republican Whip

tag: table


document_title: Everclear (alcohol)

question_text: what's the highest proof alcohol you can buy

question_tokens: what 's the highest proof alcohol you can buy

text: Everclear (alcohol)

text: Similar brands[edit]

text: Luxco also manufactures Golden Grain Alcohol as the same spirit with a different brand name. A competitor, Gem Clear, is bottled by the Quality Control Distilling Co. in Bardstown, Kentucky using roughly the same formula.

text: Alcohol content[edit]

text: Ethanol cannot be concentrated by ordinary distillation to greater than approximately 96% by weight because at that concentration, the vapor has the same ratio of water to alcohol as the liquid, a phenomenon known as azeotropy.[3] The highest concentration of ethanol generally available for human consumption is 190 proof (95% alcohol by volume), which is about 92.4% ethanol by weight.

text: In popular culture[edit]

text:
The rock band Everclear takes its name from the spirit.[4]
The Jerrod Niemann song "For Everclear" and the Roger Creager song "The Everclear Song" both refer to it.[5]
Bushwick Bill of the Geto Boys tells in his song "Ever So Clear" how drinking Everclear resulted in his eye being shot out.[6]
Everclear is the name of American Music Club's fifth album, released in 1991.
Becoming Hyderized in Hyder, Alaska. One receives a certificate for downing a shot of Everclear without pause.[7]

tag: ul


question_text: who dies in twilight breaking dawn part 2

text: Plot[edit]

text: Bella, who has just given birth, awakens from her human-to-vampire transformation and is introduced to her daughter Renesmee. The rest of the Cullens and Jacob stay nearby, and when Jacob acts possessively towards Renesmee, Bella learns he has imprinted on her, making her furious until Jacob explains what imprinting is. Meanwhile, Bella's father, Charlie, has been trying to contact the Cullens for updates on Bella's health. Carlisle comes to believe that they have to leave Forks, Washington to protect their identities - especially because of Charlie. Jacob, desperate not to lose Renesmee, visits Charlie and tell him that Bella is alive and well, but had to change in order to get better. Jacob also tells Charlie he doesn't live in the world he thinks he lives in, but says nothing about vampires. He then phases into his wolf form.  Charlie then visits the Cullen house and meets Renesmee, but doesn't know he's her biological grandfather. Afterward, the Cullens are able to stay in Forks.

text: Several months pass with Carlisle monitoring Renesmee's rapid growth. On an outing in the woods, a bitter Irina sees Renesmee from a distance and assumes she's an immortal child without asking any questions. Immortal children were vampires who were changed in childhood, and because they could not be trained nor restrained, they destroyed entire villages. They were eventually executed, as were the parents who created them, and the creation of such children outlawed. Irina goes to the Volturi to report what she has seen. Alice sees the Volturi and Irina coming to kill the Cullens, and instructs the others to gather as many witnesses as they can to testify that Renesmee is not an immortal child. The Cullens begin to summon witnesses, such as the Denali family. One of the Denali, Eleazar, later discovers that Bella has a special ability: a powerful mental shield which had protected her from Edward's mind reading even when she was human, and which she can now extend to protect others from attacks.

text: As some of their potential witnesses are attacked and prevented from supporting the Cullens, Carlisle and Edward realize they may have to fight the Volturi. Their witnesses ultimately agree to stand with them in battle, having realized the Volturi increased their Guard by falsely accusing covens of crimes, destroying them and then recruiting the vampires with gifts. The Volturi arrive prepared for battle, led by Aro, who is eager to obtain the gifted members of the Cullen coven as part of his Guard. Aro is allowed to touch Renesmee, and is convinced that she is not an immortal child. Irina is brought forth and takes full responsibility for her mistake, leading to her immediate death. Aro still insists that Renesmee may pose a risk in the future, validating his claim that battle is necessary. Before any violence, Alice shares with Aro her vision of the battle that is to come, during which both sides sustain heavy casualties, including Aro, who would also die. Aro believes her, giving Alice and Jasper an opportunity to reveal their witness, Nahuel (a half-mortal half-vampire just like Renesmee). The witness proves that he is not a threat, supporting the notion that Renesmee is not a threat. The Volturi unhappily walk away, explaining that there will be no battle today.

text: Back at the Cullen home, Alice glimpses the future, seeing Edward and Bella together with Jacob and a fully matured Renesmee also together. Edward reads Alice's mind and feels relieved that Renesmee has Jacob to protect her. Alone in the meadow, Bella pushes her mental shield away and finally allows Edward to see into her mind, showing him every moment she and Edward shared together and the two share a kiss after Bella telling Edward, "Nobody has ever loved anybody as much as I love you", and both Edward and Bella say they'll love and be together forever. The end credits present the cast members from all five films.

text: Cast[edit]

text:
Kristen Stewart as Bella Swan
Robert Pattinson as Edward Cullen
Taylor Lautner as Jacob Black
Mackenzie Foy as Renesmee Cullen
Ashley Greene as Alice Cullen
Peter Facinelli as Carlisle Cullen
Elizabeth Reaser as Esme Cullen
Kellan Lutz as Emmett Cullen
Nikki Reed as Rosalie Hale
Jackson Rathbone as Jasper Hale
Maggie Grace as Irina
Michael Sheen as Aro
Jamie Campbell Bower as Caius
Dakota Fanning as Jane
Christopher Heyerdahl as Marcus
Billy Burke as Charlie Swan
Casey LaBow as Kate
MyAnna Buring as Tanya
Lee Pace as Garrett
Christian Camargo as Eleazar
Mía Maestro as Carmen
Noel Fisher as Vladimir
Joe Anderson as Alistair
Cameron Bright as Alec
Angela Sarafyan as Tia
Rami Malek as Benjamin
Booboo Stewart as Seth Clearwater
Daniel Cudmore as Felix
Ty Olsson as Phil
Alex Meraz as Paul
Judith Shekoni as Zafrina
Charlie Bewley as Demetri
J. D. Pardo as Nahuel
Wendell Pierce as J. Jenks
Julia Jones as Leah Clearwater
Lateef Crowder as Santiago
Andrea Powell as Sasha
Toni Trucks as Mary
Andrea Gabriel as Kebi
Austin Naulty as Werewolf
Kiowa Gordon as Embry Call
Chaske Spencer as Sam Uley
Bronson Pelletier as Jared
Marisa Quinn as Huilen
Omar Metwally as Amun
Valorie Curry as Charlotte
Tracey Heggins as Senna
Marlane Barnes as Maggie
Guri Weinberg as Stefan
Erik Odom as Peter
Tyson Houseman as Quil Ateara
Gil Birmingham as Billy Black
Lisa Howard as Siobhan
Bill Tangradi as Randall
Patrick Brennan as Liam
Amadou Ly as Henri
Janelle Froehlich as Yvette
Masami Kosaka as Toshiro

text: Cam Gigandet (James), Rachelle Lefevre, and Bryce Dallas Howard (Victoria), Edi Gathegi (Laurent), Jodelle Ferland (Bree Tanner), and various other actors from the previous films make cameos during the ending credits.[6]

text: Production[edit]

text: Development[edit]

text: After confirming one film, Summit Entertainment had been keeping their eye on a fifth installment.[clarification needed] In May 2010, Billy Burke and Peter Facinelli were the only cast actors who were confirmed for both parts of Breaking Dawn, while other cast members such as Ashley Greene and Kellan Lutz were still in negotiations for a second part. If the actors holding Summit back from making an official announcement did not reach an agreement with them, the studio would not have minded recasting their roles, as was done in The Twilight Saga: Eclipse with Bryce Dallas Howard's character, Victoria. However, in June 2010, Summit officially confirmed that a two-part adaptation of the fourth book would start production and it was made clear that all major actors, including the three lead roles, the Cullen family, and Charlie Swan, would return for both parts.

text: Pre-production[edit]

text: By August 2009, Rosenberg said that the scripts for Part 1 and 2 were 75 to 85 percent completed. She found the greatest challenge in writing the scripts to be the final sequence of Part 2: "The final battle sequence is a big challenge because it lasts 25 pages", she said. "It's almost an entire three-act story in and of itself. You have to track [keep it all in one setting] hundreds of characters. It's an enormous challenge to choreograph on the page and for Bill [Condon] to choreograph on the stage." She had written various drafts of the scene but, at that, hadn't revised or discussed them with Condon yet. She said, "That's the next big hurdle to sit down with the stunt coordinator and create the ballet. It's a lot of work. I'm exhausted, but we're intent on making them the best scripts yet." Godfrey called Part 2 "an action film in terms of life-and-death stakes" and said that in Part 1 "there are the pangs of newlywed tension that occur that are relatable even in a fantasy film. Marriage is not quite the experience that they thought it was." Condon thought of Part 1 "as a real companion piece to Catherine Hardwicke's movie". Condon explains, "Like, everything that got set up there gets resolved here. I think you'll find that there are stylistic and other nods to that film."

text: Godfrey considered releasing the second film in 3D to differentiate between the time before and after Bella becomes a vampire, an idea originally proposed for Eclipse, but said that the decision is up to Condon. However, he said that if the second film were to be released in 3D, he would like to shoot it with the proper equipment in "real" 3D as was done with Avatar (2009), not convert it into 3D in post-production as was done with Clash of the Titans (2010).[7] On February 12, 2012 it was confirmed that Part 2 would not be filmed in 3D.[8]

text: Filming[edit]

text: Filming started on November 1, 2010 and wrapped, for most of the cast, on April 15, 2011, ending the franchise's three years of production since March 2008. Filming was shot on location in Baton Rouge, Louisiana; Vancouver, British Columbia; New Orleans; and at the Raleigh Studios in Baton Rouge.

text: On the subject of the final day and her final moment as Bella, Stewart stated, "After that scene, my true final scene, I felt like I could shoot up into the night sky and every pore of my body would shoot light. I felt lighter than I've ever felt in my life."[9] Pattinson thought the day was "amazing" and commented, "I then asked myself why we didn't do this in those four years. Every difficult moment just vanished."

text: In April 2012, the crew and cast, including Pattinson and Stewart, returned for reshoots to pick up some additional shots for technical work with some of the cast and stunt actors. These re-shoots did not include any new scenes or dialogue.[10]

text: Special effects[edit]

text: Tippett Studio first began working on the CGI (computer-generated imagery) wolves in February 2009 for The Twilight Saga: New Moon, and the look of the creatures has evolved, becoming more photo real over the course of the saga, with the input of three different directors. "It's a subtle balance of just how anthropomorphic these wolves are," says Eric Leven. "Bill (Condon) wanted to make sure that we had a sense of the human or the shape shifter in there. Finding that balance of how much of a human performance versus an animal performance was important for Bill."

text: Leven adds, "Bill has always treated the wolves as characters and never as computer generated things, and directs them in the same way he'd direct any actor. He would always give us direction like Sam should be angrier. It's the best way to work. His treating these creatures as characters, instead of just computer bits, was really great."

text: "Because we've been working on this franchise for such a prolonged period of time, we've been able to improve the look from show to show," comments Phil Tippett. "Wolves generally are pretty darn clean and since Bill wanted the wolves rangier, that means a lot more fur matting and clumping, like they've lived out in the woods. We edged towards something a bit more feral."

text: "However, there is also a balance between look and technology," adds Tippett. "The body count of the wolves escalates and because we're adding a great deal more hair to get the right texture, that fur really ups the rendering time. We've gone from four wolves to eight to twelve, to sixteen in Part 2. So we have to be very careful about that balance, because it takes hundreds of hours to render each wolf."[11]

text: Music[edit]

text: It was revealed in January 2012 that the soundtrack for Part 2 had already started production.[12] Confirmed for the soundtrack in advance were "Heart of Stone" by Iko, which plays when Edward and Bella are talking in the cottage after finding Alice's note and "Where I Come From" by Passion Pit, which will play when Bella wakes up from her transformation.[13] The lead single from the soundtrack is "The Forgotten", performed by the American rock band Green Day. "A Thousand Years, Pt. 2" by the American singer Christina Perri is also featured on the soundtrack album.

text: Carter Burwell, the composer of Twilight and Breaking Dawn: Part 1, returned to score the final installment of the series. In later announcements, Burwell confirmed that the score for the film was complete. "The movie basically upholds the final installment with a score that has the same jungle-music feeling The Twilight Saga: Breaking Dawn – Part 1 brought us," Burwell affirmed. "The music pieces that take place in the catalytic final battle will be very much like the nineteenth song in the previous movie's score, 'It's Renesmee' and the twenty-fourth, 'You Kill Her You Kill Me', which were, if not the most, one of the boldest pieces in my career. I will tease anything but I recommend for the fans to listen to 'A Kick in the Head', 'Exacueret Nostri Dentes in Filia' and 'Aro's End' if you want to have goosebumps for the rest of your life."[citation needed]

text: Release[edit]

text: Box office[edit]

text: The Twilight Saga: Breaking Dawn – Part 2 has earned $292,324,737 in North America and $537,360,640 in other territories for a worldwide total of $829,685,377.[3] The film is now the 46th-highest-grossing film of all time, the sixth-highest-grossing film of 2012, and the highest-grossing film of the Twilight series. It had a $340.9 million worldwide opening, which was the eighth-largest ever, the largest for the Twilight franchise, and the largest for a film released outside the summer period.[14]

text: In North America, the film grossed $30.4 million in Thursday night and midnight showings, achieving the third-highest midnight gross[15][16] and the highest midnight gross of the franchise.[17][18] Breaking Dawn – Part 2 made an $71.2 million on its opening day, which is the sixth-highest opening- and single-day gross as well as the third-highest of the franchise.[19] For its opening weekend, the movie earned $141.1 million,[20] which is the 13th-highest-grossing opening weekend of all time,[21][22] the second-highest-grossing of the franchise,[23] the third-largest November opening,[24] and the fourth-largest opening of 2012.[25] It retained first place in its second weekend by dropping 69.1% with a gross of $43.6 million over the three-day weekend and made a total of $64.4 million over the five-day Thanksgiving holiday weekend.[26] In its third weekend, Breaking Dawn Part – 2 held onto the No. 1 spot again by dropping 60.1% and grossing $17.4 million.[27] It became the third-highest-grossing film of the franchise behind Eclipse and New Moon.[28]

text: Outside North America, the film opened on Wednesday, November 14, 2012 in six countries earning $13.8 million. By Thursday, it had opened in 37 territories, earning $38.8 million. In all territories, it opened with similar or higher earnings than its immediate predecessor.[29] Through its first Friday, it earned $91.0 million, after expanding to 61 territories.[30][31] By the end of its opening weekend (Wednesday–Sunday), it scored a series-best $199.5 million opening from 61 territories on 12,812 screens. This is the eighth-largest opening outside North America and the largest 2012 opening.[32] IMAX showings generated $3 million from 82 locations.[33] The film's largest openings were recorded in the UK, Ireland, and Malta ($25.2 million), Russia and the CIS ($22.0 million), and France and the Maghreb region ($17.9 million).[34] In Spain, it set a three-day opening-weekend record with $11.9 million.[35] In total earnings, its three highest-grossing markets after North America are the UK, Ireland, and Malta ($57.9 million), Brazil ($54.2 million), and Russia and the CIS ($42.8 million).[34]

text: Critical response[edit]

text: The film received mixed reviews from critics, but the reviews were much more favorable than those of its predecessor. At Rotten Tomatoes, the film has a 48% rating, based on 185 reviews with the consensus stating: "It's the most entertaining Twilight, but that's not enough to make Breaking Dawn Part 2 worth watching for filmgoers who don't already count themselves among the franchise converts."[36] At Metacritic it has a weighted average score of 52 out of 100, based on reviews from 31 critics.[37] Audiences polled on CinemaScore gave it an average rating of 'A'.[38] The majority of praise from both fans and critics went towards the ending sequence, Michael Sheen's performance as the Volturi leader Aro and Lee Pace's performance as vampire Garrett.

text: Todd McCarthy of The Hollywood Reporter wrote, "The final installment of the immortal Bella/Edward romance will give its breathlessly awaiting international audience just what it wants".[39] Owen Gleiberman of Entertainment Weekly said, "Breaking Dawn: Part 2 starts off slow but gathers momentum, and that's because, with Bella and Edward united against the Volturi, the picture has a real threat".[40] Sara Stewart of the New York Post wrote, "Finally, someone took the source material at its terribly written word and stopped treating the whole affair so seriously".[41] Justin Chang of Variety praised the performance of Stewart by saying, "No longer a mopey, lower-lip-biting emo girl, this Bella is twitchy, feral, formidable and fully energized, a goddess even among her exalted bloodsucker brethren".[42] Manohla Dargis of The New York Times said, "Despite the slow start Mr. Condon closes the series in fine, smooth style. He gives fans all the lovely flowers, conditioned hair and lightly erotic, dreamy kisses they deserve".[43]

text: Roger Ebert of the Chicago Sun-Times gave the film two-and-a-half stars out of four, saying "its audience, which takes these films very seriously indeed, will drink deeply of its blood. The sensational closing sequence cannot be accused of leaving a single loophole, not even some of those we didn't know were there". He concluded by saying, ""Breaking Dawn, Part 2" must be one of the more serious entries in any major movie franchise… it bit the bullet, and I imagine fans will be pleased."[44] Helen O'Hara of Empire gave the film a mixed review and said, "Fans will be left on a high; other viewers will be confused but generally entertained by a saga whose romance is matched only by its weirdness".[45]

text: Home media[edit]

text: The Twilight Saga: Breaking Dawn – Part 2 was released on DVD and Blu-ray on March 2, 2013.[46] As of June 1, 2014, Breaking Dawn: Part 2 has sold 4,810,249 DVDs along with 1,224,869 Blu-ray Discs for $71,418,469 and $24,472,107 respectively totaling $99,195,325.[47]

text: Future[edit]

text: In September 2016, Lionsgate co-chairman Patrick Wachsberger stated that a sequel was "a possibility" but would only go ahead if Stephenie Meyer wanted to do one.[48] On August 8, 2017, Variety reported that Lionsgate CEO Jon Feltheimer has interest in having spinoff's made for The Twilight Saga, and wants to create a writers' room to explore the idea.[49]

text: Awards and nominations[edit]

text:
Year
Award
Category
Recipients
Result
Ref.

2013

Empire Cinemas Alternative Movie Awards

Best On-Screen Couple

Edward Cullen (Robert Pattinson) and Bella Swan (Kristen Stewart)

Won

[50]

Best On-Screen Kiss

Edward Cullen (Robert Pattinson) and Bella Swan (Kristen Stewart)

Won

Best Fight Scenes

Breaking Dawn – Part 2

Won

Best Film Villain

Aro (Michael Sheen)

Won

Best Male Body

Jacob Black (Taylor Lautner)

Won

2013

Golden Raspberry Awards

Worst Picture

Breaking Dawn – Part 2

Won

[51]

Worst Actor

Robert Pattinson

Nominated

Worst Actress

Kristen Stewart(for Breaking Dawn – Pt. 2 and Snow White and the Huntsman)

Won

Worst Supporting Actor

Taylor Lautner

Won

Worst Supporting Actress

Ashley Greene

Nominated

Worst Screen Couple

Mackenzie Foy and Taylor Lautner

Won

Robert Pattinson and Kristen Stewart

Nominated

Worst Prequel, Remake, Rip-off or Sequel

Breaking Dawn – Part 2

Won

Worst Director

Bill Condon

Won

Worst Screenplay

Melissa Rosenberg and Stephenie Meyer

Nominated

Worst Screen Ensemble

Entire cast of Breaking Dawn – Part 2

Won

2013

MTV Movie Awards

Best Shirtless Performance

Taylor Lautner

Won

[52]

2013

Moviefone Fonie Award

Most Extreme Role Adjustment

Kristen Stewart(for Breaking Dawn – Pt. 2 and On the Road)

Won

[53]

2013

Nickelodeon Kids' Choice Awards

Favorite Movie Actress

Kristen Stewart

Won

[54]

2013

Nickelodeon UK Kids' Choice Awards

Favourite UK Actor

Robert Pattinson

Won

[55]

2013

People's Choice Awards

Favorite Movie Fan Following

Twihards

Won

[56]

2013

Richard Attenborough Film Award

British Performer of the Year

Robert Pattinson

Won

[57]

2013

Virgin Media Award

Hottest Movie Actor

Robert Pattinson

Won

[58]

Hottest Movie Actress

Kristen Stewart

Won

2013

Young Artist Award

Best Performance in a Feature Film - Supporting Young Actress

Mackenzie Foy

Nominated

[59]

2013

Teen Choice Awards

Choice Romance Actress

Kristen Stewart

Won

Choice Movie Scene Stealer

Kellan Lutz

Won

Choice Sci-Fi/Fantasy Actor

Taylor Lautner

Won

Choice Sci-Fi/Fantasy Actress

Kristen Stewart

Won

Choice Sci-Fi/Fantasy

Breaking Dawn - Part 2

Won

Choice Romance Actor

Robert Pattinson

Won

Choice Romance

Breaking Dawn - Part 2

Won


document_title: Isthmus of Panama

question_text: when did the collision between north and south america take place

text: Isthmus of Panama

text: History[edit]

text: Vasco Núñez de Balboa heard of the South Sea from natives while sailing along the Caribbean coast. On 25 September 1513 he saw the Pacific. In 1519 the town of Panamá was founded near a small indigenous settlement on the Pacific coast. After the discovery of Peru, it developed into an important port of trade and became an administrative centre. In 1671 the Welsh pirate Henry Morgan crossed the Isthmus of Panamá from the Caribbean side and destroyed the city. The town was relocated some kilometers to the west at a small peninsula. The ruins of the old town, Panamá Viejo, are preserved and were declared a UNESCO World Heritage Site in 1997.

text: Silver and gold from the viceroyalty of Peru were transported overland across the isthmus by Spanish Silver Train to Porto Bello, where Spanish treasure fleets shipped them to Seville and Cádiz from 1707.

text: Lionel Wafer spent four years between 1680 and 1684 among the Cuna Indians.

text: Scotland tried to establish a settlement in 1698 through the Darien scheme.

text: The California Gold Rush, starting in 1849, brought a large increase in the transportation of people from the Atlantic to the Pacific. Steamships brought gold seekers from eastern US ports who trekked across the isthmus by foot, horse, and later rail. On the Pacific side, they boarded Pacific Mail Steamship Company vessels headed for San Francisco.

text: Ferdinand de Lesseps, the man behind the Suez Canal, started a Panama Canal Company in 1880 that went bankrupt in 1889 in a scandal.

text: In 1902–4, the United States forced Colombia to grant independence to the department of the isthmus, bought the remaining assets of the Panama Canal Company, and finished the canal in 1914.

text: Geology[edit]

text: A significant body of water (referred to as the Central American Seaway) once separated the continents of North and South America, allowing the waters of the Pacific and Atlantic Oceans to mix freely. Beneath the surface, two plates of the Earth's crust were slowly colliding, forcing the Cocos Plate to slide under the Caribbean Plate. The pressure and heat caused by this collision led to the formation of underwater volcanoes, some of which grew large enough to form islands as early as 15 million years ago. Meanwhile, movement of the two tectonic plates was also pushing up the sea floor, eventually forcing some areas above sea level.

text: Over time, massive amounts of sediment (sand, soil, and mud) from North and South America filled the gaps between the newly forming islands. Over millions of years, the sediment deposits added to the islands until the gaps were completely filled. By no later than 4.5 million years ago, an isthmus had formed between North and South America. However, in April 2015, an article in Science Magazine stated that zircon crystals in middle Miocene bedrock from northern Colombia indicated that by 10 million years ago, it is likely that instead of islands, a full isthmus between the North and South American continents had already likely formed where the Central American Seaway had been previously.[4]

text: Evidence also suggests that the creation of this land mass and the subsequent warm, wet weather over northern Europe resulted in the formation of a large Arctic ice cap and contributed to the current ice age. That warm currents can lead to glacier formation may seem counterintuitive, but heated air flowing over the warm Gulf Stream can hold more moisture. The result is increased precipitation that contributes to snow pack.

text: The formation of the Isthmus of Panama also played a major role in biodiversity on the planet. The bridge made it easier for animals and plants to migrate between the two continents. This event is known in paleontology as the Great American Interchange. For instance, in North America today, the opossum, armadillo, and porcupine all trace back to ancestors that came across the land bridge from South America. Likewise, bears, cats, dogs, horses, llamas, and raccoons all made the trek south across the isthmus.

text: Biosphere[edit]

text: As the connecting bridge between two vast land masses, the Panamanian biosphere is filled with overlapping fauna and flora from both North and South America. There are, for example, over 978[5] species of birds in the isthmus area. The tropical climate also encourages a myriad of large and brightly colored species, insects, amphibians, birds, fish, and reptiles. Divided along its length by a mountain range, the isthmus's weather is generally wet on the Atlantic (Caribbean) side but has a clearer division into wet and dry seasons on the Pacific side.


document_title: Mongol invasion of Rus'

question_text: who threw off the rule of the mongols

question_tokens: who threw off the rule of the mongols

text: Mongol invasion of Rus'

text: Background[edit]

text: As it was undergoing fragmentation, Kievan Rus' faced the unexpected eruption of an irresistible foreign foe coming from the mysterious regions of the Far East. "For our sins", writes the Rus' chronicler of the time, "unknown nations arrived. No one knew their origin or whence they came, or what religion they practiced. That is known only to God, and perhaps to wise men learned in books".[7]

text: The princes of Rus' first heard of the coming Mongol warriors from the nomadic Cumans. Previously known for pillaging settlers on the frontier, the nomads now preferred peaceful relations, warning their neighbors: "These terrible strangers have taken our country, and tomorrow they will take yours if you do not come and help us". In response to this call, Mstislav the Bold and Mstislav Romanovich the Old joined forces and set out eastward to meet the foe, only to be routed on April 1, 1223 at the Battle of the Kalka River.

text: Although this defeat left the Rus' principalities at the mercy of invaders, the Mongol forces retreated and did not reappear for thirteen years, during which time the princes of Rus' went on quarrelling and fighting as before, until they were startled by a new and much more formidable invading force. In the Secret History of the Mongols, the only reference to this early battle is:

text: "Then he (Chinghis Khan) sent Dorbei the Fierce off against the city of Merv, and on to conquer the people between Iraq and the Indus. He sent Subetei the Brave off to war in the North where he defeated eleven kingdoms and tribes, crossing the Volga and Ural Rivers, finally going to war with Kiev."

text: Invasion of Batu Khan[edit]

text: The vast Mongol hordes of around 35,000[citation needed] mounted archers, commanded by Batu Khan and Subutai, crossed the Volga River and invaded Volga Bulgaria in late 1236. It took them only a month to extinguish the resistance of the weak Volga Bulgarians, the Cumans-Kipchaks and the Alani.

text: In November 1237, Batu Khan sent his envoys to the court of Yuri II of Vladimir and demanded his submission. A month later, the hordes besieged Ryazan. After six days of bloody battle, the city was totally annihilated and inhabitants slaughtered.[5] Alarmed by the news, Yuri II sent his sons to detain the invaders, but they were defeated and ran for their lives. Having burnt down Kolomna and Moscow, the horde laid siege to Vladimir on February 4, 1238. Three days later, the capital of Vladimir-Suzdal was taken and burnt to the ground. The royal family perished in the fire, while the grand prince retreated northward. Crossing the Volga, he mustered a new army, which was encircled and totally annihilated by the Mongols in the Battle of the Sit River on March 4.

text: Thereupon Batu Khan divided his army into smaller units, which ransacked fourteen cities of modern-day Russia: Rostov, Uglich, Yaroslavl, Kostroma, Kashin, Ksnyatin, Gorodets, Galich, Pereslavl-Zalessky, Yuriev-Polsky, Dmitrov, Volokolamsk, Tver and Torzhok. Chinese siege engines were used by the Mongols under Tului to raze the walls of Russian cities.[8] The most difficult to take was the small town of Kozelsk, whose boy-prince Vasily, son of Titus, and inhabitants resisted the Mongols for seven days, killing 4,000. As the story goes, at the news of the Mongol approach, the whole town of Kitezh with all its inhabitants was submerged into a lake, where, as legend has it, it may be seen to this day. The only major cities to escape destruction were Novgorod and Pskov. The Mongols planned to advance on Novgorod, but the principality was spared the fate of its brethren by the wise decision to preemptively surrender.[9]

text: In mid-1238, Batu Khan devastated the Crimea and pacified Mordovia. In the winter of 1239, he sacked Chernigov and Pereyaslav. After many days of siege, the horde stormed Kiev in December 1240. Despite the resistance of Danylo of Halych, Batu Khan managed to take two of his principal cities, Halych and Volodymyr-Volynskyi. The Mongols then resolved to "reach the ultimate sea", where they could proceed no further, and invaded Hungary (under Batu Khan) and Poland (under Baidar and Kaidu).[5] Batu Khan captured Pest, and then on Christmas Day 1241, Esztergom.[5]

text: Age of Tatar rule[edit]

text: This time the invaders came to stay, and they built for themselves a capital, called Sarai, on the lower Volga. Here the commander of the Golden Horde, as the western section of the Mongol empire was called, fixed his golden headquarters and represented his sovereign the grand khan who lived with the Great Horde in the Orkhon Valley. Here they had their headquarters and held parts of Rus' in subjection for nearly three centuries. All of the Russian states, including Novgorod, Smolensk, Galich and Pskov, submitted to the Tatar-Mongol rule.[10]

text: The term by which this subjection is commonly designated, the Mongol or Tatar "yoke", suggests terrible oppression, but in reality these nomadic invaders from Mongolia were not such cruel, oppressive taskmasters.[11] In the first place, they never settled in the country, and they had little direct dealing with the inhabitants. In accordance with the admonitions of Genghis Khan to his children and grandchildren, they retained their pastoral mode of life, so that the subject races, agriculturists and dwellers in towns were not disturbed in their ordinary avocations. Golden Horde instituted census, taxes and tributes on the conquered lands, which were usually collected by local princes and brought to Sarai. It was only in the 14th and 15th centuries, with the rise of the Tatar khanates, that slave raids on the Slavic population became significant, with the purpose of trading slaves with the Ottoman Empire. The raids were an important drain of the human and economic resources of both Muscovy and the Grand Duchy of Lithuania, and they largely prevented the settlement of the "Wild Fields" – the steppe and forest-steppe land extending from about a hundred miles south of Moscow to the Black Sea – and they ultimately contributed to the development of the Cossacks.

text: In religious matters, the Mongols were extremely tolerant. When they first appeared in Europe, they were shamanists, and as such they had no religious fanaticism. After adopting Islam they remained as tolerant as before,[12] and the khan of the Golden Horde, who first became a Muslim, allowed the Rus' to found a Christian bishopric in his capital. Nogai Khan, half a century later, married a daughter of the Byzantine emperor and gave his own daughter in marriage to a Rus' prince, Theodor the Black. Some modern revisionist Russian historians (most notably the Soviet era historian and "Neo-Eurasianist" ideologist Lev Gumilev) even postulate that there was no invasion at all. According to them, the Rus' princes concluded a defensive alliance with the Horde in order to repel attacks of the fanatical Teutonic Knights, which posed a much greater threat to the Rus' religion and culture.

text: These points represent the bright side of Tatar rule, but it also had its dark side. So long as a great horde of nomads was encamped on the frontier, the country was liable to be invaded by an overwhelming force. Fortunately, these invasions were not frequent, but when they occurred they caused an incalculable amount of devastation and suffering. In the intervals the people had to pay a fixed tribute. At first it was collected in a rough-and-ready fashion by Tatar tax-gatherers; by about 1259 it was regulated by a census of the population; and finally its collection was entrusted to the native princes, so the people were no longer brought into direct contact with the Tatar officials.

text: Impact on development[edit]

text:
Part of a series on the

History of East Slavs

Middle Ages

Early East Slavs
Khazars
Rus' Khaganate
Kievan Rus'
Novgorod Republic
Vladimir-Suzdal
Galicia–Volhynia
Mongol invasion
Golden Horde
Grand Duchy of Lithuania
Grand Duchy of Moscow

Early Modern period

Tsardom of Russia
Cossack Hetmanate
Polish–Lithuanian Commonwealth

Modern period

Russian Empire
Revolutions of 1917
Russian Civil War
Soviet Union

Post-Soviet states

Belarus
Russian Federation
Ukraine

History of states

History of Belarus
History of Russia
History of Ukraine

v
t
e

text: The influence of the Mongol invasion on the territories of Kievan Rus' was uneven. Colin McEvedy (Atlas of World Population History, 1978) estimates the population of Kievan Rus' dropped from 7.5 million prior to the invasion to 7 million afterwards.[3] Centers such as Kiev took centuries to rebuild and recover from the devastation of the initial attack. The Novgorod Republic continued to prosper, and new entities, the rival cities of Moscow and Tver, began to flourish under the Mongols. Moscow's eventual dominance of northern and eastern Rus' was in large part attributable to the Mongols. After the prince of Tver joined a rebellion against the Mongols in 1327, his rival prince Ivan I of Moscow joined the Mongols in crushing Tver and devastating its lands. By doing so he eliminated his rival, allowed the Russian Orthodox Church to move its headquarters to Moscow and was granted the title of Grand Prince by the Mongols. As such, the Muscovite prince became the chief intermediary between the Mongol overlords and the Rus' lands, which paid further dividends for Moscow's rulers. While the Mongols often raided other areas of Rus', they tended to respect the lands controlled by their principal collaborator. This, in turn, attracted nobles and their servants who sought to settle in the relatively secure and peaceful Moscow lands.[13]

text: Although Rus' forces defeated the Golden Horde at the Battle of Kulikovo in 1380, Mongol domination of parts of Rus' territories, with the requisite demands of tribute, continued until the Great stand on the Ugra river in 1480.

text: Historians argued[by whom?] that without the Mongol destruction of Kievan Rus', the Rus' would not have unified into the Tsardom of Russia and, subsequently, the Russian Empire would not have risen. Trade routes with the East went through Rus' territory, making them a center of trade between east and west. Mongol influence, while destructive to their enemies, had a significant long-term effect on the rise of modern Russia, Ukraine and Belarus.[14]

text: Historiography[edit]

text: The Mongol conquest of Rus' left a deep mark on Russian historiography. The ability of pagan nomads from inner Asia to subjugate Russia is according to Charles J. Halperin a source of embarrassment among the "educated Russian society".[15] This embarrassment is thought to be a contributing cause to the emergence of New Chronology pseudohistory that claims the conquest is a forgery.[15]

text: Influence on Rus' society[edit]

text: Historians have debated the long-term influence of Mongol rule on Rus' society. The Mongols have been blamed for the destruction of Kievan Rus', the breakup of the ancient Rus' nationality into three components and the introduction of the concept of "oriental despotism" into Russia.[citation needed] Historians also credit the Mongol regime with an important role in the development of Muscovy as a state. Under Mongol occupation, for example, Muscovy developed its mestnichestvo hierarchy, postal road network (based on Mongolian ortoo system, known in Russian as "yam", hence the terms yamshchik, Yamskoy Prikaz, etc.), census, fiscal system and military organization.[16]

text: The period of Mongol rule over Russia included significant cultural and interpersonal contacts between the Russian and Mongolian ruling classes. By 1450, the Tatar language had become fashionable in the court of the Grand Prince of Moscow, Vasily II, who was accused of excessive love of the Tatars and their speech, and many Russian noblemen adopted Tatar surnames (for example, a member of the Veliamanov family adopted the Turkic name "Aksak" and his descendants were the Aksakovs)[17] Many Russian boyar (noble) families traced their descent from the Mongols or Tatars, including Veliaminov-Zernov, Godunov, Arseniev, Bakhmetev, Bulgakov (descendents of Bulgak) and Chaadaev (descendents of Genghis Khan's son Chagatai Khan). In a survey of Russian noble families of the 17th century, over 15% of the Russian noble families had Tatar or Oriental origins.[18]

text: The Mongols brought about changes in the economic power of states and overall trade. In the religious sphere, St. Paphnutius of Borovsk was the grandson of a Mongol baskak, or tax collector, while a nephew of Khan Bergai of the Golden Horde converted to Christianity and became known as the monk St. Peter Tsarevich of the Horde.[19] In the judicial sphere, under Mongol influence capital punishment, which during the times of Kievan Rus' had only been applied to slaves, became widespread, and the use of torture became a regular part of criminal procedure. Specific punishments introduced in Moscow included beheading for alleged traitors and branding of thieves (with execution for a third arrest).[20]


document_title: Economy of Buffalo, New York

question_text: what is the main industry in buffalo ny

question_tokens: what is the main industry in buffalo ny

text: Economy of Buffalo, New York

text: History[edit]

text: Buffalo and the surrounding area were long involved in railroad commerce, steel manufacture, automobile production, aircraft/aerospace design and production, Great Lakes shipping, and grain storage. Most of these industries have left the city through the years. Major steel production no longer exists in the area, although several smaller steel mills remain in operation. For example, Gibraltar Industries, a leading manufacturer, processor, and distributor of steel products for the building, industrial, and vehicular markets is headquartered in Buffalo. As of the 1950 United States Census, Buffalo was the 15th largest city in the country, the nation's largest inland port (twelfth overall), second biggest rail center, sixth largest steel producer, and eighth largest manufacturer.[2]

text: Employment[edit]

text: Overall, employment in Buffalo has shifted as its population has declined and manufacturing has diminished. Buffalo's 2005 unemployment rate was 6.6%, contrasted with New York State's 5.0% rate.[3] And from the fourth quarter of 2005 to the fourth quarter of 2006, Erie County had no net job growth, ranking it 271st among the 326 largest counties in the country.[4] Yet the area has recently seen an upswing in job growth as unemployment has dropped to only 4.9% in July 2007 from 5.2% in 2006 and 6.6% in 2005.[5] The area's manufacturing jobs have continued to show the largest losses in jobs with over 17,000 fewer than at the start of 2006. Yet other sectors of the economy have outdistanced manufacturing and are seeing large increases. Educational and health services added over 30,400 jobs in 2006 and over 20,500 jobs have been added in the professional and business (mostly finance) arena.[6]

text: Life sciences[edit]

text: Buffalo has increasingly become a center for bioinformatics and human genome research, including work by researchers at the University at Buffalo and the Roswell Park Cancer Institute. This consortium is known as the Buffalo Niagara Medical Campus. It also includes: Buffalo Hearing & Speech Center, Buffalo Medical Group Foundation, Hauptman-Woodward Medical Research Institute, Kaleida Health, Olmsted Center for the Visually Impaired, Cleveland BioLabs and Upstate New York Transplant Services. The DNA samples used in The Human Genome Project were also collected from anonymous donors from Buffalo.

text: Entrepreneurial resources and life science business consultants accelerate the growth and development of emerging companies found within the Buffalo Niagara Medical Campus and Upstate New York Region. For example, Buffalo BioSciences is a technology commercialization partner to the New York State Center of Excellence in Bioinformatics & Life Sciences and contributed to the launch and early success of Empire Genomics –- a firm based on research conducted at Roswell Park Cancer Institute by Dr. Norma Nowak[7] enabling the delivery of personalized medicine.

text: Banking[edit]

text: Buffalo is the headquarters of M&T Bank, a large regional bank with assets over $79B (as of June 2011).[8] HSBC Bank USA has reduced its local operations in Buffalo, and Upstate NY as a whole, as it closed its retail banking centers. Many of the shuttered HSBC retail banking centers in upstate were acquired by First Niagara Bank (see below). Other banks, such as Bank of America and KeyBank have corporate operations in Buffalo. Citigroup also has regional offices in Amherst, Buffalo's largest suburb. Buffalo has also become a hub of the debt collection industry.[9]

text: First Niagara Bank recently moved its headquarters to downtown Buffalo from nearby Lockport. First Niagara has branches from Buffalo to Albany, New York, and since September 2009 has had branches as far south as Pittsburgh. On September 10, 2009, First Niagara announced the relocation of its corporate headquarters from Lockport to downtown Buffalo. The company says facilities in Lockport will remain open and fully staffed.[10] First Niagara, which had been considering expanding into Western Pennsylvania for some time,[11] benefited from PNC Financial Services being required by the United States Department of Justice to sell off 50 National City branches in the Pittsburgh area and 11 more branches in and around Erie to competitors,[12] since the two banks had significant overlap in Western Pennsylvania and had potential antitrust issues in that area. First Niagara took advantage by buying 57 of the 61 National City branches from PNC that had to be divested after PNC acquired National City with funds from the $700 billion bailout plan after National City became a victim of the subprime mortgage crisis. The move affected the area by creating 200 more jobs, some in the Buffalo area.[13] On July 31, 2011, it was announced First Niagara had acquired all of HSBC Banks Western New York branches; after closing and selling some branches to its competitors its total number in Upstate New York had almost doubled.[14]

text: Other[edit]

text: Buffalo is home to Rich Products, one of the world's largest family-owned food manufacturers.[15] Canadian brewer Labatt moved its US headquarters to Buffalo in May 2007.[16] This is in large part due to Buffalo's location directly in the middle of the Northeastern Trade Corridor. The city is the heart of the Canadian-American corridor. Over 80% of all U.S.-Canada trade occurs via border crossings in the eastern United States and with five bridges to Canada, the Buffalo area is one of the key eastern border crossing locations. Cheese company Sorrento Lactalis is also based in Buffalo.

text: New Era Cap Company, the largest sports-licensed headwear company in the United States, is based in Buffalo. It opened new headquarters in 2007 in the former Federal Reserve Building in downtown Buffalo.[17]

text: The windshield wiper maker Trico, founded in Buffalo by John R. Oishei, operated three major manufacturing facilities but has since closed all of them and moved operations to Mexico. In 1998, the company head office moved to Rochester Hills, Michigan.[18] Trico's Plant No. 1 was placed on the National Register of Historic Places in 2001 and in 2014 was being re-developed by the State University of New York at Buffalo. The John R. Oishei Foundation is western New York's largest and the new Women's & Children's Hospital, scheduled to open in 2015, will be named the John R. Oishei Children's Hospital.

text: For many years, Buffalo was the nation's second largest rail center, after Chicago. Peaked traffic reached during World War II, but declined soon after the war.[19] Through the 1960s and 1970s freight traffic via Buffalo declined, air travel and the New York State Thruway took railway passengers away as well.[19] By 1980, the rail hub in the city was gone.[19]

text: Del Monte Foods' Milk Bone dog biscuits are still manufactured in a small factory on the city's East Side.

text: Regionally based insurance companies also have maintained their headquarters in Buffalo, New York. There's Merchants Insurance Group and Lawley Insurance. Merchants Insurance Group is a property and casualty insurance company that provides commercial, personal property and casualty insurance throughout the Northeast and North Central United States. Lawley Insurance provides commercial insurance, employee benefits, risk management and personal insurance.

text: Delaware North Companies are headquartered in Buffalo.[20]

text: Standard of living[edit]

text: The loss of traditional jobs in manufacturing, rapid suburbanization and high costs of labor have led to economic decline, making Buffalo one of the poorest among U.S. cities with populations of more than 250,000 people. An estimated 28.7–29.9% of Buffalo residents live below the poverty line, behind either only Detroit,[21] or only Detroit and Cleveland.[22] Buffalo's median household income of $27,850 is third-lowest among large cities, behind only Miami and Cleveland; however the median household income for the metropolitan area is $57,000.[23]

text: This, in part, has led to the Buffalo-Niagara Falls metropolitan area having the most affordable housing market in the U.S. today. The quarterly NAHB/Wells Fargo Housing Opportunity Index (HOI) noted that nearly 90% of the new and existing homes sold in the metropolitan area during the second quarter were affordable to families making the area's median income of $57,000. The area median price of homes was $75,000.[citation needed]

text: Buffalo faces issues with vacant and abandoned houses, as the city ranks second to St. Louis on the list of American cities with the most vacant properties per capita. Since 2000, the city has torn down 2,000 vacant homes but as many as 10,000 still remain. Mayor Byron W. Brown recently unveiled a $100 million, five-year plan to demolish 5,000 more houses.[24] The city's move away from heavy industry and toward a service and bioinformatics economy[citation needed] has brought improved air and water quality, which benefit not only residents and tourists but the bioregion as a whole. In July 2005, Reader's Digest ranked Buffalo as the third cleanest large city in the nation.[25]

text: Buffalo's economy has begun to see significant improvements since the early 2010s.[26] Money from state governor Andrew Cuomo, plans for different construction programs, and hundreds of new jobs have brought strong economic change to the area.[27]

text: Principal employers[edit]

text: According to the City's 2013 Comprehensive Annual Financial Report,[28] the principal employers in the Buffalo Metropolitan Area are:

text:
#
Employer
# of Employees

1
State of New York
15,123

2
Federal Executive Board (United States of America)
11,183

3
Kaleida Health
10,000

4
University at Buffalo
6,733

5
Catholic Health System
6,628

6
Employer Services Corp
6,363

7
M&T Bank
5,140

8
Tops Markets
5,058

9
Buffalo City School District
4,949

10
Erie County
4,203